Regulation of Stat3 nuclear export.
Regulation of Stat3 nuclear export.
复制标题
DOI：
10.1172/jci15372
复制
发表时间：
2003-02
期刊：
影响因子：
--
通讯作者：
S. Bhattacharya;C. Schindler
中科院分区：
文献类型：
--
作者：
S. Bhattacharya;C. Schindler
STAT3是信号转导和转录激活因子(STAT)转录因子家族中最具多效性的成员，介导细胞因子家族的关键反应。在静息细胞中，包括STAT3在内的STATs主要存在于细胞质中。在细胞因子的刺激下，它们迅速移位到细胞核，在那里它们促进了靶基因的表达。在随后的信号衰变期间，它们被重新输出到细胞质中，为下一轮信号传递做准备。这一核出口过程可被真菌毒素瘦素B(LMB)阻断。与STAT1的情况相反，LMB处理不仅阻止了刺激后STAT3从细胞核回到细胞质的输出，而且还促进了STAT3在静止细胞中的核积累。值得注意的是，依赖LMB的STAT3在静息细胞中的核积累不依赖于酪氨酸磷酸化，这突显了存在一条“基本的”信号通路。随后的研究确定了三个核出口信号(NES)元素。其中两个元件，STAT3(306-318)和STAT3(404-414)，对应于最近在STAT1中发现的那些元件，第三个元件，STAT3(524-)，是新的。STAT3(306-318)在刺激后的快速核输出(刺激后输出)中起重要作用，而STAT3(404-414)和STAT3(524-)在调节基础核输出中起更重要的作用。综上所述，这些研究表明，STAT3核出口过程依赖于多种NES元素。
Stat3 is the most pleiotropic member of the signal transducer and activator of transcription (STAT) family of transcription factors and mediates pivotal responses for the cytokine family. In resting cells, STATs, including Stat3, reside largely in the cytoplasm. Upon cytokine stimulation, they rapidly translocate to the nucleus, where they promote the expression of target genes. During the subsequent period of signal decay they are re-exported back to the cytoplasm in preparation for the next round of signaling. This process of nuclear export can be blocked by the fungal toxin leptomycin B (LMB). In contrast to what appears to be the case for Stat1, LMB treatment not only blocks the poststimulation export of Stat3 from the nucleus back to the cytoplasm, but also promotes the nuclear accumulation of Stat3 in resting cells. Remarkably, the LMB-dependent nuclear accumulation of Stat3 in resting cells is independent of tyrosine phosphorylation, highlighting the existence of a "basal" signaling pathway. Subsequent studies identified three nuclear export signal (NES) elements. Two of these elements, Stat3(306-318) and Stat3(404-414), corresponded to those recently identified in Stat1, and a third, Stat3(524-535), is novel. Stat3(306-318) appears to be important in the rapid nuclear export seen after stimulation (poststimulation export), whereas the Stat3(404-414) and Stat3(524-535) play a more important role in regulating basal nuclear export. In summary, these studies indicate that the process of Stat3 nuclear export is dependent on multiple NES elements.